UBQLN1
ubiquilin 1, the group of Ubiquilin family
Basic information
Region (hg38): 9:83659968-83707958
Links
Phenotypes
GenCC
Source:
- intellectual disability (Limited), mode of inheritance: AD
ClinVar
This is a list of variants' phenotypes submitted to
Variants pathogenicity by type
Statistics on ClinVar variants can assist in determining whether a specific variant type in the UBQLN1 gene is commonly pathogenic or not.
In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.
Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.
| Variant type | Pathogenic | Likely pathogenic | VUS | Likely benign | Benign | Sum |
|---|---|---|---|---|---|---|
| synonymous | 8 | |||||
| missense | 9 | |||||
| nonsense | 0 | |||||
| start loss | 0 | |||||
| frameshift | 1 | |||||
| inframe indel | 0 | |||||
| splice donor/acceptor (+/-2bp) | 0 | |||||
| splice region | 0 | |||||
| non coding | 0 | |||||
| Total | 0 | 1 | 8 | 8 | 1 |
Variants in UBQLN1
This is a list of pathogenic ClinVar variants found in the UBQLN1 region.
You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.
| Position | Type | Phenotype | Significance | ClinVar |
|---|---|---|---|---|
| 9-83661867-C-A | not specified | Uncertain significance (Jul 08, 2022) | ||
| 9-83663963-T-C | not specified | Uncertain significance (Apr 09, 2024) | ||
| 9-83665031-C-G | not specified | Uncertain significance (Dec 15, 2021) | ||
| 9-83665109-G-C | not specified | Uncertain significance (Jan 25, 2023) | ||
| 9-83666356-G-A | Benign (Apr 06, 2018) | |||
| 9-83666364-T-C | not specified | Uncertain significance (Nov 13, 2023) | ||
| 9-83666416-G-A | Likely benign (Jan 12, 2018) | |||
| 9-83669197-G-A | Likely benign (Dec 31, 2019) | |||
| 9-83669284-T-C | Likely benign (Mar 29, 2018) | |||
| 9-83677755-A-C | Likely benign (May 04, 2018) | |||
| 9-83677768-C-A | Likely benign (Jan 01, 2023) | |||
| 9-83677875-T-C | Likely benign (Jan 02, 2018) | |||
| 9-83680012-C-T | Likely benign (Jun 26, 2018) | |||
| 9-83683021-AT-A | Abnormal brain morphology | Likely pathogenic (-) | ||
| 9-83683022-T-C | not specified | Uncertain significance (Feb 06, 2023) | ||
| 9-83707518-C-A | Uncertain significance (May 15, 2018) | |||
| 9-83707612-G-A | not specified | Uncertain significance (Aug 11, 2022) | ||
| 9-83707620-G-C | Likely benign (Mar 28, 2018) | |||
| 9-83707625-C-T | not specified | Uncertain significance (Jun 03, 2022) | ||
| 9-83707627-G-A | not specified | Uncertain significance (Jun 24, 2022) |
GnomAD
Source:
| Gene | Type | Bio Type | Transcript | Coding Exons | Length |
|---|---|---|---|---|---|
| UBQLN1 | protein_coding | protein_coding | ENST00000376395 | 11 | 48241 |
| pLI Probability LOF Intolerant | pRec Probability LOF Recessive | Individuals with no LOFs | Individuals with Homozygous LOFs | Individuals with Heterozygous LOFs | Defined | p |
|---|---|---|---|---|---|---|
| 0.999 | 0.00116 | 125683 | 0 | 4 | 125687 | 0.0000159 |
| Z-Score | Observed | Expected | Observed/Expected | Mutation Rate | Total Possible in Transcript | |
|---|---|---|---|---|---|---|
| Missense | 2.39 | 194 | 313 | 0.620 | 0.0000149 | 3887 |
| Missense in Polyphen | 55 | 133.8 | 0.41106 | 1680 | ||
| Synonymous | -0.436 | 113 | 107 | 1.05 | 0.00000516 | 1134 |
| Loss of Function | 4.60 | 2 | 28.4 | 0.0703 | 0.00000139 | 308 |
LoF frequencies by population
| Ethnicity | Sum of pLOFs | p |
|---|---|---|
| African & African-American | 0.0000294 | 0.0000294 |
| Ashkenazi Jewish | 0.00 | 0.00 |
| East Asian | 0.00 | 0.00 |
| Finnish | 0.00 | 0.00 |
| European (Non-Finnish) | 0.0000177 | 0.0000176 |
| Middle Eastern | 0.00 | 0.00 |
| South Asian | 0.0000329 | 0.0000327 |
| Other | 0.00 | 0.00 |
dbNSFP
Source:
- Function
- FUNCTION: Plays an important role in the regulation of different protein degradation mechanisms and pathways including ubiquitin- proteasome system (UPS), autophagy and endoplasmic reticulum- associated protein degradation (ERAD) pathway. Mediates the proteasomal targeting of misfolded or accumulated proteins for degradation by binding (via UBA domain) to their polyubiquitin chains and by interacting (via ubiquitin-like domain) with the subunits of the proteasome (PubMed:15147878). Plays a role in the ERAD pathway via its interaction with ER-localized proteins UBXN4, VCP and HERPUD1 and may form a link between the polyubiquitinated ERAD substrates and the proteasome (PubMed:19822669, PubMed:18307982). Isoform 1, isoform 2 and isoform 3 play a role in unfolded protein response (UPR) by attenuating the induction of UPR-inducible genes, DDTI3/CHOP, HSPA5 and PDIA2 during ER stress (PubMed:18953672). Involved in the regulation of macroautophagy and autophagosome formation; required for maturation of autophagy- related protein LC3 from the cytosolic form LC3-I to the membrane- bound form LC3-II and may assist in the maturation of autophagosomes to autolysosomes by mediating autophagosome- lysosome fusion (PubMed:19148225, PubMed:20529957, PubMed:23459205). Negatively regulates the TICAM1/TRIF-dependent toll-like receptor signaling pathway by decreasing the abundance of TICAM1 via the autophagic pathway (PubMed:21695056). Isoform 1 and isoform 3 play a key role in the regulation of the levels of PSEN1 by targeting its accumulation to aggresomes which may then be removed from cells by autophagocytosis (PubMed:21143716). Promotes the ubiquitination and lysosomal degradation of ORAI1, consequently downregulating the ORAI1-mediated Ca2+ mobilization (PubMed:23307288). Suppresses the maturation and proteasomal degradation of amyloid beta A4 protein (A4) by stimulating the lysine 63 (K63)-linked polyubiquitination. Delays the maturation of A4 by sequestering it in the Golgi apparatus and preventing its transport to the cell surface for subsequent processing (By similarity). {ECO:0000250|UniProtKB:Q9JJP9, ECO:0000269|PubMed:18307982, ECO:0000269|PubMed:18953672, ECO:0000269|PubMed:19148225, ECO:0000269|PubMed:19822669, ECO:0000269|PubMed:20529957, ECO:0000269|PubMed:21143716, ECO:0000269|PubMed:21695056, ECO:0000269|PubMed:23307288, ECO:0000269|PubMed:23459205, ECO:0000303|PubMed:15147878}.;
- Pathway
- Protein processing in endoplasmic reticulum - Homo sapiens (human);Vesicle-mediated transport;gamma-aminobutyric acid receptor life cycle pathway;Membrane Trafficking;Clathrin-mediated endocytosis;CXCR4-mediated signaling events;Cargo recognition for clathrin-mediated endocytosis
(Consensus)
Recessive Scores
- pRec
- 0.311
Intolerance Scores
- loftool
- 0.117
- rvis_EVS
- -0.31
- rvis_percentile_EVS
- 31.93
Haploinsufficiency Scores
- pHI
- 0.492
- hipred
- Y
- hipred_score
- 0.840
- ghis
- 0.614
Essentials
- essential_gene_CRISPR
- N
- essential_gene_CRISPR2
- N
- essential_gene_gene_trap
- N
- gene_indispensability_pred
- E
- gene_indispensability_score
- 0.879
Gene Damage Prediction
| All | Recessive | Dominant | |
|---|---|---|---|
| Mendelian | Medium | Medium | Medium |
| Primary Immunodeficiency | Medium | Medium | Medium |
| Cancer | Medium | Medium | Medium |
Mouse Genome Informatics
- Gene name
- Ubqln1
- Phenotype
- homeostasis/metabolism phenotype; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan);
Gene ontology
- Biological process
- autophagosome assembly;macroautophagy;ubiquitin-dependent ERAD pathway;regulation of protein ubiquitination;positive regulation of protein ubiquitination;negative regulation of toll-like receptor 3 signaling pathway;response to endoplasmic reticulum stress;aggrephagy;cellular response to hypoxia;autophagosome maturation;negative regulation of store-operated calcium channel activity;regulation of oxidative stress-induced intrinsic apoptotic signaling pathway;positive regulation of ER-associated ubiquitin-dependent protein catabolic process
- Cellular component
- proteasome complex;nucleoplasm;cytoplasm;autophagosome;endoplasmic reticulum;cytosol;plasma membrane;aggresome;cytoplasmic vesicle;protein-containing complex;perinuclear region of cytoplasm
- Molecular function
- protein binding;kinase binding;polyubiquitin modification-dependent protein binding;identical protein binding